Currently, transplantation therapy and reconstructive surgical therapy are mainly practiced in surgical medicine, but there is a persistent problem of unavailability of sufficient donors, and these therapies have a larger load on patients and often demanded repeated surgery. For these reasons, a third therapy, i.e., regeneration therapy, is attracting attention and highly expected.
In organs relatively simpler in structure such as skin, bone, and cartilage, a culture method in combination of the stem cell in the patient's organ and a biodegradable base material is effective, and some of such methods are already in the phase of clinical test. However, the regeneration therapy for complicated body organs that are structured by various kinds of cells and an extracellular matrix and that demand supply of nutrition through the blood vessel, such as of liver, kidney and pancreas, are still in the basic research phase. One reason for the delay in research on complicated body organs is a problem in conversion of the cells into a three-dimensional structure.
Cell organization is a scientific region actively studied in the regeneration therapy field. Studies on cell organization are grossly grouped into studies on two-dimensional cell sheet by using a heat-sensitive-polymer-grafted culture dish and those on lamination of multiple kinds of cells. In Japan, Okano et al. of Tokyo Women's Medical Univ. are studying co-culture of vascular endothelial cell and hepatocyte cell by using a micropatterned graft surface of a heat-sensitive polymer and reported that it was possible to form a two-dimensional co-culture cell sheet (Non-patent Documents 1, 2 and 3). In abroad, Desai et al. in Boston University reported a three-dimensional cell organization of a laminate of three kinds of cells formed on the patterning surface of PDMS stamp (Non-patent Document 4).
However, it was not possible to achieve the three-dimensional organization by the cell sheet method, and, in the case of lamination only of cells, such as that reported by Desai et al., cell migration results in random mixing, non-control of organization. Recently, three-dimensional culture of cells in a revolving incubator is often carried out, but the cell proliferation leads to increase in cell density and also difficulty in supplying nutrients, causing a problem of death in internal cells. As described above, studies on three-dimensional organization of cells are still in the early basic research level, and there is currently no basic finding desirable for three-dimensional organization, and thus, there is an urgent need for a method to solve the problems.
On the other hand, studies on three-dimensional culture-organization by using a hydrogel (base material) of polylactic acid or collagen were actively in progress in the past ten years in Japan and abroad. These hydrogels have favorable cell adhesiveness, but the cells are grown too densely in the later phase of cell culture, resulting in inhibition of internal supply of nutrients by the dense network structure of hydrogel at the millimeter and micrometer level and thus, causing a problem of death of internal cells. Further, it is reported that polylactic acid hydrogels remain in the body as implanted for one year or more without decomposition, possibly causing inflammation and tumor generation. It is necessary to control the degradability of the base material to solve these problems.
However, up to now, there is no report on the method of controlling freely decomposition of the base material for a three-dimensional cell culture and constructing and safety collecting cellular structures.    Non-patent Document 1: Y. Tsuda et al., J. Biomed. Mater. Res. 69A, 70-78 (2004)    Non-patent Document 2: Y. Tsuda et al., Biomaterials 26, 1885-93 (2005)    Non-patent Document 3: A. Maya et al., Biomaterials 23, 1121-1130 (2002)    Non-patent Document 4: W. Tan. et al., Biomaterials 25, 1355 (2004)